Melanoma is a disease in which malignant (cancer) cells form in melanocytes (cells that color the skin).

The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. Skin also helps control body temperature and stores water, fat, and vitamin D. The skin has several layers, but the two main layers are the epidermis (upper or outer layer) and the dermis (lower or inner layer). Skin cancer begins in the epidermis, which is made up of three kinds of cells:

Squamous cells: Thin, flat cells that form the top layer of the epidermis.

Melanocytes: Cells that make melanin and are found in the lower part of the epidermis. Melanin is the pigment that gives skin its natural color. When skin is exposed to the sun or artificial light, melanocytes make more pigment and cause the skin to darken.

The number of new cases of melanoma has been increasing over the last 40 years. Melanoma is most common in adults, but it is sometimes found in children and
adolescents. (See the PDQ summary on Unusual Cancers of Childhood Treatment for more information on melanoma in children and adolescents.)

Anatomy of the skin, showing the epidermis, dermis, and subcutaneous tissue. Melanocytes are in the layer of basal cells at the deepest part of the epidermis.

There are different types of cancer that start in the skin.

Melanoma is a rare form of skin cancer. It is more likely to invade nearby tissues and spread to other parts of the body than other types of skin cancer. When melanoma starts in the skin, it is called cutaneous melanoma. Melanoma may also occur in mucous membranes (thin, moist layers of tissue that cover surfaces such as the lips). This PDQ summary is about cutaneous (skin) melanoma and melanoma that affects the mucous membranes.

Unusual moles, exposure to sunlight, and health history can
affect the risk of melanoma.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk.

Risk factors for melanoma include the
following:

Having a fair complexion, which includes the following:

Fair skin that freckles and burns easily, does not tan, or tans poorly.

Blue or green or other light-colored eyes.

Red or blond hair.

Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time.

Being exposed to certain factors in the environment (in the air, your home or workplace, and your food and water). Some of the environmental risk factors for melanoma are radiation, solvents, vinyl chloride, and PCBs.

Having a history of many blistering sunburns, especially as a child or teenager.

Tests that examine the skin are used to detect (find) and
diagnose melanoma.

If a mole or pigmented area of the skin changes or looks abnormal,
the following tests and procedures can help find and diagnose
melanoma:

Skin exam: A doctor or nurse checks the skin for moles, birthmarks, or other pigmented areas that look abnormal in color,
size, shape, or texture.

Biopsy: A procedure to remove the abnormal tissue and a small amount of normal tissue around it. A pathologist looks at the tissue under a microscope to check for cancer cells. It can be hard to tell the difference between a colored mole and an early melanoma lesion. Patients may want to have the sample of tissue checked by a second pathologist. If the abnormal mole or lesion is cancer, the sample of tissue may also be tested for certain gene changes.

It is important that abnormal areas of the skin not be shaved off or
cauterized (destroyed with a hot
instrument, an electric current, or a caustic substance) because cancer cells that remain may grow and spread.

After melanoma has been diagnosed, tests are done to find out
if cancer cells have spread within the skin or to other parts of the body.

The process used to find out whether cancer has spread within the skin or to other parts
of the body is called staging. The
information gathered from the staging process determines the stage of the
disease. It is important to know the stage in order to plan treatment.

The following tests and procedures may be used in the staging
process:

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

CT scan (CAT
scan): A procedure that makes a series of detailed pictures of areas inside the body taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. For melanoma,
pictures may be taken of the chest, abdomen, and pelvis.

PET scan (positron
emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).

Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. For melanoma, the blood is checked for an enzyme called lactate dehydrogenase (LDH). LDH levels that are higher than normal may be a sign of melanoma.

The results of these tests are viewed together with the results of
the tumor biopsy to find out the stage of the melanoma.

There are three ways that cancer spreads in the body.

Tissue. The cancer spreads from where it began by growing into nearby areas.

Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.

Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.

Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if melanoma spreads to the lung, the cancer cells in the lung are actually melanoma cells. The disease is metastatic melanoma, not lung cancer.

The method used to stage melanoma is based mainly on the thickness of the tumor and whether cancer has spread to lymph nodes or other parts of the body.

The staging of melanoma depends on the following:

The thickness of the tumor. The thickness is described using the Breslow scale.

Recurrent Melanoma

Recurrentmelanoma is cancer that has recurred
(come back) after it has been treated. The cancer may come back in the area where it first started or in other parts of the body, such as the lungs or liver.

There are different types of treatment for patients with
melanoma.

Different types of treatment are available for patients with
melanoma. Some treatments are
standard (the currently used treatment), and some are being tested in
clinical trials. A
treatment clinical trial is a research study meant to help improve current
treatments or obtain information on new treatments for patients with cancer.
When clinical trials show that a new treatment is better than the
standard treatment, the new
treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Even if the doctor removes all the melanoma that can be seen at
the time of surgery, some patients may be given chemotherapy after surgery to kill
any cancer cells that are left. Chemotherapy given after surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).

One type of regional chemotherapy is hyperthermicisolated limb perfusion. With this method, anticancer drugs go directly to the arm or leg the cancer is in. The flow of blood to and from the limb is temporarily stopped with a tourniquet. A warm solution with the anticancer drug is put directly into the blood of the limb. This gives a high dose of drugs to the area where the cancer is.

The way the chemotherapy is given depends on the type and stage of the cancer being treated.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used to treat melanoma, and may also be used as palliative therapy to relieve symptoms and improve quality of life.

Immunotherapy

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or biologic therapy.

The following types of immunotherapy are being used in the treatment of melanoma:

Immune checkpoint inhibitor. Checkpoint proteins, such as B7-1/B7-2 on tumor cells and CTLA-4 on T cells, help keep immune responses in check. The binding of B7-1/B7-2 to CTLA-4 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of B7-1/B7-2 to CTLA-4 with an immune checkpoint inhibitor (anti-B7-1/B7-2 or anti-CTLA-4) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitor. Checkpoint proteins, such as B7-1/B7-2 on tumor cells and CTLA-4 on T cells, help keep immune responses in check. The binding of B7-1/B7-2 to CTLA-4 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of B7-1/B7-2 to CTLA-4 with an immune checkpoint inhibitor (anti-B7-1/B7-2 or anti-CTLA-4) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitor. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitor. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitortherapy: Some types of immune cells, such as T cells, and some cancer cells have certain proteins, called checkpoint proteins, on their surface that keep immune responses in check. When cancer cells have large amounts of these proteins, they will not be attacked and killed by T cells. Immune checkpoint inhibitors block these proteins and the ability of T cells to kill cancer cells is increased. They are used to treat some patients with advanced melanoma or tumors that cannot be removed by surgery.

There are two types of immune checkpoint inhibitor therapy:

Immune checkpoint inhibitor. Checkpoint proteins, such as B7-1/B7-2 on tumor cells and CTLA-4 on T cells, help keep immune responses in check. The binding of B7-1/B7-2 to CTLA-4 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of B7-1/B7-2 to CTLA-4 with an immune checkpoint inhibitor (anti-B7-1/B7-2 or anti-CTLA-4) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitor. Checkpoint proteins, such as B7-1/B7-2 on tumor cells and CTLA-4 on T cells, help keep immune responses in check. The binding of B7-1/B7-2 to CTLA-4 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of B7-1/B7-2 to CTLA-4 with an immune checkpoint inhibitor (anti-B7-1/B7-2 or anti-CTLA-4) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitor. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel).

Immune checkpoint inhibitor. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel).

CTLA-4 inhibitor: CTL4-A is a protein on the surface of T cells that helps keep the body’s immune responses in check. When CTLA-4 attaches to another protein called B7 on a cancer cell, it stops the T cell from killing the cancer cell. CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill cancer cells. Ipilimumab is a type of CTLA-4 inhibitor.Immune checkpoint inhibitor. Checkpoint proteins, such as B7-1/B7-2 on tumor cells and CTLA-4 on T cells, help keep immune responses in check. The binding of B7-1/B7-2 to CTLA-4 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of B7-1/B7-2 to CTLA-4 with an immune checkpoint inhibitor (anti-B7-1/B7-2 or anti-CTLA-4) allows the T cells to kill tumor cells (right panel).

PD-1 inhibitor: PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. When PD-1 attaches to another protein called PDL-1 on a cancer cell, it stops the T cell from killing the cancer cell. PD-1 inhibitors attach to PDL-1 and allow the T cells to kill cancer cells. Pembrolizumab and nivolumab are types of PD-1 inhibitors.Immune checkpoint inhibitor. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel).

Interferon: Interferon affects the division of cancer cells and can slow tumor growth.

Tumor necrosis factor (TNF) therapy: TNF is a protein made by white blood cells in response to an antigen or infection. TNF is made in the laboratory and used as a treatment to kill cancer cells. It is being studied in the treatment of melanoma.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to attack cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. The following types of targeted therapy are used or being studied in the treatment of melanoma:

Vemurafenib, dabrafenib, trametinib, and cobimetinib are signal transduction inhibitors used to treat some patients with advanced melanoma or tumors that cannot be removed by surgery. Vemurafenib and dabrafenib block the activity of proteins made by mutant BRAF genes. Trametinib and cobimetinib affect the growth and survival of cancer cells.

Oncolytic virus therapy: A type of targeted therapy that is used in the treatment of melanoma. Oncolytic virus therapy uses a virus that infects and breaks down cancer cells but not normal cells. Radiation therapy or chemotherapy may be given after oncolytic virus therapy to kill more cancer cells.

Angiogenesis inhibitors: A type of targeted therapy that is being studied in the treatment of melanoma. Angiogenesis inhibitors block the growth of new blood vessels. In cancer treatment, they may be given to prevent the growth of new blood vessels that tumors need to grow.

New targeted therapies and combinations of therapies are being studied in the treatment of melanoma.

New types of treatment are being tested in clinical trials.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Stage 0 (Melanoma in Situ)

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage 0 melanoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI website.

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I melanoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI website.

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage II melanoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI website.

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III melanoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI website.

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage IV melanoma and recurrent melanoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI website.

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